MULTIPARAMETRIC MRI OF CARTILAGE

准确评估软骨结构和功能完整性的非破坏性技术对于确定关节炎的自然病程以及评估预防和治疗干预措施的效果至关重要。我们的长期目标是建立用于评估关节软骨成分和功能完整性的磁共振成像(MRI)技术。在该奖项的第一个周期中，我们使用磁共振波谱研究来演示和表征几个旨在测量重要软骨特性的磁共振可测量参数的敏感性。我们发现水的扩散率对软骨结构敏感，磁化传递(MT)对胶原含量和结构敏感，钠离子浓度可以用来定量GAG浓度。此外，对白细胞介素1和胰酶降解的比较研究揭示了多参数方法在单项测量中的威力。然后，我们专注于在成像模式下应用磁共振。考虑到磁共振成像钠的困难，我们首先致力于开发一种基于质子的磁共振方法来测量Gag浓度。由此产生的技术得到了广泛的验证。软骨GAG技术的空间和时间变化的高分辨率图像被广泛验证。软骨GAG的空间和时间变化的高分辨率图像突出了当可以获得组织成分的空间分布时可获得的更多信息。最后，证明了该技术在体内(临床)检测人类软骨中GAG变异的可行性和有效性。下一个周期的总体目标是探索成像模式下的其他MR参数，并将它们结合起来进行多参数MRI研究。本研究的具体目的是：(1)比较培养牛软骨诱导降解和再生过程中MRI参数的时空分布。(2)将多参数磁共振成像方法应用于自然疾病不同阶段的人体组织。(3)使用所开发的磁共振方法识别有或不存在胶原和/或GAG异常的人软骨区域，并在培养中监测这些样本。(4)多参数磁共振成像技术在组织工程软骨构建中的应用。因此，这些研究的长期结果应该会产生前所未有的机会，以非破坏性的方式监测活组织中关键软骨成分的空间分布和时间演变，在离体软骨中，以接近组织学分辨率和临床相关分辨率进行研究，这些研究以前是不可行的。

Non-destructive techniques for accurately assessing the structural and functional integrity of cartilage are essential for defining the natural history of arthritis and for evaluating the effects of prevention and therapeutic interventions. Our long term goal is to establish magnetic resonance imaging (MRI) techniques for evaluating the compositi0nal and functional integrity of articular cartilage. In the first cycle of this award, we used MR spectroscopy studies to demonstrate and characterize the sensitivity of several MR measurable parameters designed to measure important cartilage properties. We demonstrated that diffusivity of water was sensitive to cartilage structure; magnetization transfer (MT) was sensitive to collagen content and structure, and sodium concentrat6ion could be used to quantify GAG concentration. Furthermore, comparative studies of interleukin-1 and trypsin degradation revealed the power of a multiparametric approach over individual measurements We then focused on applying MR in an imaging mode. Given the difficulties in imaging sodium by MR, we first focused on developing a proton based MR method for measuring GAG concentration. The resulting technique was extensively validated. High resolution images of spatial and temporal variations in cartilage GAG technique was extensively validated. High resolution images of spatial and temporal variations in cartilage GAG highlighted the increased information available when the spatial distribution of tissue constituents can be obtained. Finally, the in vivo (clinical) feasibility and validity of this technique to detect variations in GAG in human cartilage was demonstrated. The overall aim of this next cycle is to explore the other MR parameters in an imaging mode and combine them for a multiparametric MRI study. The specific aims of this proposal are: (1) To compare the spatial and temporal distribution of the set of MRI parameters during induced degradation and regeneration of bovine cartilage in culture. (2) To apply the multi multiparametric MRI approach to human tissue in different stages of natural disease. (3) To use the developed MR measures to identify areas of human cartilage with and without identified collagen and/or GAG abnormalities, and monitor these samples in culture. (4) To develop and apply the multiparametric MRI approach to tissue engineered cartilage constructs. The long term results of these studies should therefore yield the unprecedented opportunity to non-destructively monitor the spatial distribution and temporal evolution of critical cartilage constituents in living tissue at near-histologic resolution in isolated cartilage and at clinically relevant resolutions in vivo, studies which were previously not feasible.